Genetic effects such as transvection (the interallelic complementation that is dependent on chromosome pairing) and the zeste-white effect, show that interactions occur between chromosome regions separated by many tens of kb or located on different chromosomes. A protagonist in these effects is the product of the zeste gene. We have cloned the zeste gene, isolated its product and raised antibodies against it. We have shown that zeste binds to DNA at multiple, specific sites in the white gene and several other complex genes such as Ubx, dpp and Antp. The DNA binding sites and their distribution in these genetic loci and along the polytene chromosomes suggested to us that zeste interactions may provide a means of bringing distant regulatory regions of complex loci such as Ubx in contact with the promoter. We will use genetic and molecular approaches to test this hypothesis and to study the role of the zeste gene in the functioning of the large class of genes with which it appears to associate. We propose to study the protein chemistry of the zeste product, its mutants and variant proteins produced by manipulating the gene. We will characterize its interactions with DNA, its recognition sequence and the relationship of its binding sites to other regulatory sites. The effect of zeste binding at these sites on transcription will be studied both in vitro and in vivo. We will examine the interaction of zeste with other nuclear structures in vivo and in vitro and its associations with other proteins. Among these we expect to find the products of suppressor of zeste loci of which we propose to clone one or more. The model we propose has important implications for the interplay of distant genomic regions as well as the regulation of complex loci not only in Drosophila but in other organisms which we will examine for the presence of similar functions.